Brossaud Julie, Ducint Dominique, Corcuff Jean-Benoît
Department of Nuclear Medicine, CHU de Bordeaux, Pessac, France.
Nutrition et Neurobiologie intégrée, UMR 1286, University of Bordeaux, Pessac, France.
Clin Endocrinol (Oxf). 2016 Feb;84(2):236-243. doi: 10.1111/cen.12717. Epub 2015 Feb 20.
Total urinary cortisol metabolites represent cortisol production and metabolism. We hypothesized that to assay metabolites could add some information to the one provided by a sole cortisol assay.
We set up an inexpensive multiplex mass spectrometry assay to quantify cortisol metabolites. We investigated 43 patients with benign secreting (AT+) or silent (AT-) adrenal tumours compared to 48 lean (Nl) or 143 obese (Ob) subjects, and to 26 patients with a Cushing's disease (CD). The initial investigation included immunoreactive quantification of urinary free cortisol (UFC).
Cortisol metabolites were overexcreted in CD but not in Ob subjects. Nl and Ob were thus pooled in a control population (Ctl). Cortisol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE) excretions were significantly increased in AT compared to Ctl subjects, whereas immunoreactive UFC was similar. A logistic regression retaining cortisol, THF, and α- and β-cortolone as significant analytes allowed the construction of a receiver-operating characteristics (ROC) curve significantly better than the curve generated by cortisol alone (area under the curve (AUC) 0·927 vs 0·729, respectively; P < 0·0001). More importantly, although there was no significant difference between Ctl vs AT- subjects for cortisol metabolites, a logistic regression retaining cortisol, allo-THF, and α- and β-cortolone as significant analytes generated a ROC curve performing significantly better than cortisol alone (AUC 0·910 vs 0·635, respectively; P < 0·0001).
Cortisol metabolite excretion is modified in AT, including AT-, patients even without modification of UFC. Clinical usefulness of these biomarkers has to be investigated in prospective studies following up patients with AT.
尿中皮质醇代谢产物总量代表皮质醇的产生和代谢。我们推测，检测代谢产物可为仅检测皮质醇所提供的信息增添一些内容。
我们建立了一种低成本的多重质谱分析法来定量皮质醇代谢产物。我们研究了43例患有良性分泌性（AT+）或无功能（AT-）肾上腺肿瘤的患者，并与48例瘦人（Nl）或143例肥胖者（Ob）以及26例库欣病（CD）患者进行了比较。初始检查包括对尿游离皮质醇（UFC）进行免疫反应定量。
皮质醇代谢产物在CD患者中排泄过多，但在Ob受试者中未出现这种情况。因此，将Nl和Ob合并为一个对照人群（Ctl）。与Ctl受试者相比，AT患者的皮质醇、四氢皮质醇（THF）和四氢可的松（THE）排泄量显著增加，而免疫反应性UFC相似。一项逻辑回归分析保留了皮质醇、THF以及α-和β-皮质酮作为显著分析物，由此构建的受试者工作特征（ROC）曲线明显优于仅由皮质醇生成的曲线（曲线下面积（AUC）分别为0·927和0·729；P < 0·0001）。更重要的是，尽管Ctl与AT-受试者在皮质醇代谢产物方面无显著差异，但一项保留皮质醇、别-THF以及α-和β-皮质酮作为显著分析物的逻辑回归分析生成的ROC曲线表现明显优于仅由皮质醇生成的曲线（AUC分别为0·910和0·635；P < 0·0001）。
在包括AT-患者在内的AT患者中，即使UFC没有改变，皮质醇代谢产物的排泄也会发生改变。这些生物标志物的临床实用性必须在前瞻性研究中对AT患者进行随访时加以研究。
